Thiopurine S-methyltransferase pharmacogenetics: autophagy as a mechanism for variant allozyme degradation.

ABSTRACT:

Objective

Thiopurine S-methyltransferase (TPMT)*3A is degraded much more rapidly than is the 'wild-type' enzyme through a ubiquitin-proteasome-dependent process. It also forms aggresomes, suggesting a possible dynamic balance between degradation and aggregation. We set out to identify genes encoding proteins participating in these processes.

Methods

Green fluorescent protein tagged TPMT*3A was expressed in a Saccharomyces cerevisiae gene deletion library, and flow cytometry was used to screen for cells with high fluorescence intensity, indicating the loss of a gene essential for TPMT*3A degradation.

Results

Twenty-four yeast genes were identified in functional categories that included ubiquitin-dependent protein degradation, vesicle trafficking, and vacuolar degradati

SUBMITTER: Li F 

PROVIDER: S-EPMC2583164 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature